Epidemiologic data suggest that maternal microbial infections may cause fetal neurodevelopmental disorders, potentially increasing susceptibility to heavy psychopathologies such as schizophrenia, schizophreniform disorder, autism, pervasive developmental disorders, bipolar disorders, psychosis, epilepsy, language and speech disorders, and cognitive impairment in adult offspring. However, the molecular pathomechanisms underlying such a relationship are not clear. Here we analyze the potential role of the maternal immune response to viral infection in determining fetal brain injuries that increase the risk of neurological disorders in the adult. We use influenza infection as a disease model and human axon guidance pathway, a key process in the formation of neural network during midgestation, as a potential fetal target of immune insults. Specifically, we examined influenza A H1N1 hemagglutinin (HA), an antigenic viral protein, for amino acid sequence similarity to a random library of 188 axon guidance proteins. We obtain the results that (1) contrary to any theoretical expectations, 45 viral pentapeptide matches are distributed throughout a subset of 36 guidance molecules; (2) in 24 guidance proteins, the peptide sharing with HA antigen involves already experimentally validated influenza HA epitopes; and (3) most of the axon guidance vs HA peptide overlap is conserved among influenza A viral strains and subsets. Taken together, our data indicate that immune cross-reactivity between influenza HA and axon guidance molecules is possible and may well represent a pathologic mechanism capable of determining neurodevelopmental disruption in the fetus.

Our previous research and a comprehensive meta-analysis of data from the literature on epitope mapping has revealed that the B cell epitope repertoire is allocated to rare peptide motifs, i.e., antigenic peptide sequences endowed with a low level of similarity to the host proteome. From a clinical point of view, low-similarity peptides able to evoke an immune response appear to be of special interest for the rational design of vaccines for poorly treatable diseases such as hepatitis-C virus (HCV) infection. Indeed, low similarity peptides would guarantee the highest specificity and lowest cross-reactivity, i.e., effectiveness without adverse side-effects. In this study, aimed at gaining further information for the development of effective anti-HCV peptide-based vaccines, the HCV epitopes recognized by human antibodies and currently catalogued in the Immune Epitope Data Base (IEDB) were examined for pentamer sequence similarities to the human proteome. We report that the analyzed HCV determinants are characterized by the presence of fragment absent from (or scarcely represented in) human proteins. These data confirm the low-similarity hypothesis, according to which a low-similarity to the host proteome defines the nonself character of microbial antigens and modulates peptide immunogenicity. Moreover, this study indicates a concrete and safe immunotherapeutic approach which might be used in a universal anti-HCV vaccine.

Epstein-Barr virus proteins were examined for amino acid sequence matching to human proteins at the decapeptide level. We report that numerous EBV peptides of different length (from 10- to 13-mer) are present in 28 human proteins. The viral vs. human peptide overlap mainly involves the glycine-rich region allocated in the NH2 terminus of Epstein-Barr nuclear antigen 1 protein and host cellular components that play crucial roles in basic biochemical pathways, such as chromatin remodeling, RNA splicing, transmission across chemical/electrical synapses, and neurogenesis, and that, when altered, may characterize various pathologies such as immunodeficiency, systemic lupus erythematosus, myelination, and speech disorders. The present results might contribute to understand and define the (physio) pathological relationships and interactions occurring between EBV and the human host.

No abstract

BackgroundSalmonella spp. and oxyurids are among the most prevalent bacterial and parasitic agents in reptiles. These organisms are routinely isolated in healthy tortoises, although heavy infections may cause significant pathology. Tortoises are considered a common source of reptile-associated salmonellosis, an important zoonosis reported worldwide. A survey of the prevalence of Salmonella spp. and oxyurids in 53 tortoises was conducted in southern Italy and a possible correlation between the two pathogens was therefore investigated.ResultsSalmonella spp. and oxyurids were detected with a prevalence of 49.1 and 81.1%, respectively. A significant positive correlation between Salmonella spp. and oxyurids was demonstrated. However, confounding factors related to husbandry could have been involved in determining this correlation.ConclusionsOur results suggest that caution should be exercised in translocation, husbandry, and human contact with tortoises and other exotic pets. Further studies on the epidemiology, molecular characterization and pathogenesis of Salmonella and oxyurids are needed to assess the actual impact of these organisms, as single or associated infections, on tortoises and on other exotic pets.

The objective of this study was to assess local vascular architecture in atrophic-erosive oral lichen planus (OLP)

Epstein-Barr virus (EBV) infects B-, T-, and NK cells and has been associated not only with a wide range of lymphoid malignancies but also with autoimmune diseases such as lupus erythematosus, rheumatoid arthritis and, in particular, multiple sclerosis. Hence, effective immunotherapeutic approaches to eradicate EBV infection might overthrow cancer and autoimmunity incidence. However, currently no effective anti-EBV immunotherapy is available. Here we use the concept that protein immunogenicity is allocated in rare peptide sequences and search the Epstein-Barr nuclear antigen 1 (EBNA1) sequence for peptides unique to the viral protein and absent in the human host. We report on a set of unique EBV EBNA1 peptides that might be used in designing peptide-based therapies able to specifically hitting the virus or neutralizing pathogenic autoantibodies.

BackgroundWe study the usage of specific peptide platforms in protein composition. Using the pentapeptide as a unit of length, we find that in the universal proteome many pentapeptides are heavily repeated (even thousands of times), whereas some are quite rare, and a small number do not appear at all. To understand the physico-chemical-biological basis underlying peptide usage at the proteomic level, in this study we analyse the energetic costs for the synthesis of rare and never-expressed versus frequent pentapeptides. In addition, we explore residue bulkiness, hydrophobicity, and codon number as factors able to modulate specific peptide frequencies. Then, the possible influence of amino acid composition is investigated in zero- and high-frequency pentapeptide sets by analysing the frequencies of the corresponding inverse-sequence pentapeptides. As a final step, we analyse the pentadecamer oligodeoxynucleotide sequences corresponding to the never-expressed pentapeptides.ResultsWe find that only DNA context-dependent constraints (such as oligodeoxynucleotide sequence location in the minus strand, introns, pseudogenes, frameshifts, etc.) provide a coherent mechanistic platform to explain the occurrence of never-expressed versus frequent pentapeptides in the protein world.ConclusionsThis study is of importance in cell biology. Indeed, the rarity (or lack of expression) of specific 5-mer peptide modules implies the rarity (or lack of expression) of the corresponding n-mer peptide sequences (with n < 5), so possibly modulating protein compositional trends. Moreover the data might further our understanding of the role exerted by rare pentapeptide modules as critical biological effectors in protein-protein interactions.